Lian Haifeng, Zhong Xiaoying S, Xiao Ying, Sun Zhe, Shen Yuanyuan, Zhao Kaile, Ma Xingbin, Li Yanmin, Niu Qiong, Liu Max, Powell Don W, Liu Chengxia, Li Qingjie
Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China.
Division of Gastroenterology, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX, United States.
Front Mol Biosci. 2022 Feb 22;9:759689. doi: 10.3389/fmolb.2022.759689. eCollection 2022.
While the interplay between heart and gut in inflammatory bowel disease (IBD) has previously been noted, how the inflamed gut impairs heart function remain elusive. We hypothesized that exosomal miRNAs of gut origin induce cardiac remodeling in IBD. Our aim was to identify plasma exosomal miRNAs that not only are of diagnostic value but also contribute to cardiac remodeling in patients with ulcerative colitis (UC). Plasma exosomes were isolated from UC patients and healthy control subjects and exosomal miRNAs were profiled by next-generation sequencing. Exosomal miR-29b levels in CCD841 CoN colon epithelial cells were detected by RT-qPCR. Exosomes packaged with miR-29b were incubated with H9c2 cells or administered to live mice. The plasma exosomal miRNA profiles of the UC patients were significantly different from that of the controls and 20 miRNAs including miR-29b were differentially expressed. In CCD841 CoN cells, TNFα, IL-1β, and HO significantly elevated miR-29b in both the cells and their secreted exosomes ( < 0.01), suggesting that intestinal epithelium secrets exosomes rich in miR-29b in IBD. In H9c2 myoblast cells, miR-29b modulated multiple genes including brain-derived neurotrophic factor (BDNF). Epithelial cell-derived exosomes packaged with miR-29b also attenuated BDNF and increased cleaved caspase 3, suggestive of apoptosis. Furthermore, tail vein injection of engineered exosomes with high levels of miR-29b suppressed BDNF and augmented cleaved caspase 3 in the heart of adult mouse ( < 0.01). Plasma exosomal miRNA profile could be a novel diagnostic approach for IBD. Excessive plasma exosomal miR-29b suppresses critical proteins like BDNF in IBD, leading to cardiac impairment.
虽然先前已注意到炎症性肠病（IBD）中心脏与肠道之间的相互作用，但炎症性肠道如何损害心脏功能仍不清楚。我们假设源自肠道的外泌体微小RNA（miRNA）会在IBD中诱导心脏重塑。我们的目的是鉴定血浆外泌体miRNA，其不仅具有诊断价值，而且还会促使溃疡性结肠炎（UC）患者发生心脏重塑。从UC患者和健康对照受试者中分离血浆外泌体，并通过下一代测序分析外泌体miRNA。通过RT-qPCR检测CCD841 CoN结肠上皮细胞中外泌体miR-29b的水平。将包装有miR-29b的外泌体与H9c2细胞一起孵育或给予活小鼠。UC患者的血浆外泌体miRNA谱与对照组有显著差异，包括miR-29b在内的20种miRNA差异表达。在CCD841 CoN细胞中，肿瘤坏死因子α（TNFα）、白细胞介素-1β（IL-1β）和HO显著提高了细胞及其分泌的外泌体中的miR-29b（<0.01），这表明在IBD中肠上皮分泌富含miR-29b的外泌体。在H9c2成肌细胞中，miR-29b调节多个基因，包括脑源性神经营养因子（BDNF）。包装有miR-29b的上皮细胞来源的外泌体也会使BDNF减少并增加裂解的半胱天冬酶3，提示细胞凋亡。此外，尾静脉注射高水平miR-29b的工程化外泌体可抑制成年小鼠心脏中的BDNF并增加裂解的半胱天冬酶3（<0.01）。血浆外泌体miRNA谱可能是IBD的一种新型诊断方法。IBD中过量的血浆外泌体miR-29b会抑制像BDNF这样的关键蛋白，导致心脏损伤。
